2-{3-[2,2-Difluoro-2-(4-fluoronaphthyl)acetylamino]-2-fluoro-6-nitrophenyl]ethyl Acetate → 2-[2-Amino-5-[2,2-difluoro-2-(4-fluoronaphthyl)acetylamino]-6-fluorophenyl}ethyl Acetate

HRID 1060221Notes

Reaction equation

HRID 1060221 reaction equation
[C:1]([O:4][CH2:5][CH2:6][C:7]1[C:12]([N+:13]([O-])=O)=[CH:11][CH:10]=[C:9]([NH:16][C:17](=[O:32])[C:18]([F:31])([F:30])[C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]([F:29])=[CH:21][CH:20]=2)[C:8]=1[F:33])(=[O:3])[CH3:2]>C(O)C.C1COCC1.[Pd]>[C:1]([O:4][CH2:5][CH2:6][C:7]1[C:8]([F:33])=[C:9]([NH:16][C:17](=[O:32])[C:18]([F:30])([F:31])[C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]([F:29])=[CH:21][CH:20]=2)[CH:10]=[CH:11][C:12]=1[NH2:13])(=[O:3])[CH3:2]

Participants

5

Reactant 1

HCID 224753272-{3-[2,2-Difluoro-2-(4-fluoronaphthyl)acetylamino]-2-fluoro-6-nitrophenyl]ethyl Acetate

Product 1

HCID 224753342-[2-Amino-5-[2,2-difluoro-2-(4-fluoronaphthyl)acetylamino]-6-fluorophenyl}ethyl AcetateYield 83.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-{3-[2,2-difluoro-2-(4-fluoronaphthyl)acetylamino]-2-fluoro-6-nitrophenyl}ethyl acetate (4.9 g, 10.5 mmol), as prepared in the preceding step, and Pd/C (10%, 500 mg) in ethanol (50 mL) and THF (50 mL) was stirred under hydrogen for 5 hours. The reaction mixture was filtered through Celite, and washed with THF and MeOH. The filtrate and washings were combined, concentrated in vacuo, and flash chromatographed on silica gel eluting with EtOAc/DCM (0 to 2%) to produce the title compound (3.8 g, 83%) as an off white solid. 1H-NMR (400 MHz, CDCl3) δ 8.27 (d, J=8.2 Hz, 1H), 8.19 (d, J=8.6 Hz, 1H), 8.10 (s, 1H), 7.82 (m, 2H), 7.63 (m, 2H), 7.19 (t, J=8.6 Hz, 1H), 6.46 (d, J=8.7 Hz, 1H), 4.19 (t, J=7.4 Hz, 2H), 4.08 (s, 2H), 2.91(t, J=7.3 Hz, 2H), 2.08 (s, 3H).

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. washwashed with THF and MeOH
  3. concentrationconcentrated in vacuo, and flash
  4. customchromatographed on silica gel eluting with EtOAc/DCM (0 to 2%)

Sources & evidence

ORD record
ord-fdede8ac61a54c7cb83ffa5f470bb546
Source dataset
uspto-grants-2003_02
Patent number
US06521663B2

Reaction notes

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